Variant 11-89911942-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001384911.1(TRIM49D1):c.1004C>T(p.Thr335Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000052 ( 0 hom., cov: 16)

Exomes 𝑓: 0.000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49D1
NM_001384911.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00200

Variant links:

Genes affected

TRIM49D1 (HGNC:43973): (tripartite motif containing 49D1) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM49D1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04635498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49D1	NM_001384911.1 linkuse as main transcript	c.1004C>T	p.Thr335Ile	missense_variant	8/8	ENST00000420869.3	NP_001371840.1
TRIM49D1	NM_001206627.2 linkuse as main transcript	c.1004C>T	p.Thr335Ile	missense_variant	7/7		NP_001193556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TRIM49D1	ENST00000420869.3 linkuse as main transcript	c.1004C>T	p.Thr335Ile	missense_variant	8/8	5	NM_001384911.1	ENSP00000474678	P2
TRIM49D1	ENST00000605881.5 linkuse as main transcript	c.773C>T	p.Thr258Ile	missense_variant	6/6	1		ENSP00000479562	A2
TRIM49D1	ENST00000530311.6 linkuse as main transcript	c.1004C>T	p.Thr335Ile	missense_variant	8/8	5		ENSP00000474850	P2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

114836

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000371

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00138

GnomAD3 exomes

AF:

0.0000325

AC:

AN:

30734

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

16946

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000275

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000161

AC:

AN:

933542

Hom.:

Cov.:

AF XY:

0.0000108

AC XY:

AN XY:

464332

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000483

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000544

Gnomad4 OTH exome

AF:

0.0000986

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000522

AC:

AN:

114896

Hom.:

Cov.:

AF XY:

0.0000555

AC XY:

AN XY:

54060

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000371

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00136

Alfa

AF:

0.000142

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2022

The c.1004C>T (p.T335I) alteration is located in exon 6 (coding exon 6) of the TRIM49D1 gene. This alteration results from a C to T substitution at nucleotide position 1004, causing the threonine (T) at amino acid position 335 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.28

CADD

Benign

4.4

DANN

Benign

0.67

DEOGEN2

Benign

0.037

T;.;T

FATHMM_MKL

Benign

0.0072

LIST_S2

Benign

0.70

.;T;.

M_CAP

Benign

0.012

MetaRNN

Benign

0.046

T;T;T

PrimateAI

Uncertain

0.51

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.40

B;.;B

Vest4

0.13

MVP

0.22

GERP RS

-0.75

Varity_R

0.060

gMVP

0.029

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over